Nod2 is both a positive and negative regulator of Tlr4 - the effect it exerts is dependent on the presence of MDP. Nod2 upon engagement with its ligand, MDP, positively regulates Tlr4-mediated signaling; in the absence of MDP, Nod2 negatively regulates the Tlr4 pathway.

Nod1 and Nod2 synergize with Tlr4 in dendritic cells to increase IL12 production and enhance invariant natural killer T (iNKT) cell activation, and are important regulators of the IFN gamma response by iNKT cells during S. typhimurium and L. monocytogenes infections.

[Homo sapiens] NOD2-dependent recognition of S. aureus and muramyl dipeptide is facilitated by alpha-toxin (alpha-hemolysin), a pore-forming toxin and virulence factor of the pathogen and is dependent on IL-1beta-amplified production of IL-6.

[Homo sapiens] NOD2 is both a positive and negative regulator of TLR4 - the effect it exerts is dependent on the presence of MDP. NOD2 upon engagement with its ligand, MDP, positively regulates TLR4-mediated signalling; in the absence of MDP, NOD2 negatively regulates the TLR4 pathway. (Demonstrated in murine model)

[Homo sapiens] NOD2 is a peripheral peptidoglycan intracellular sensor and is important for the progression and pathogenesis of experimental autoimmune encephalomyelitis (animal model of multiple sclerosis).

[Homo sapiens] Following NOD2 activation, IRF4 interacts with MYD88, TRAF6, and RIPK2 and downregulates K63-linked polyubiquitinylation of RICK and TRAF6 leading to disruption of NFkB activation pathways.

[Homo sapiens] NOD2 plays a role in intestinal innate immunity by regulating the expression of DEFA5 and DEFA6 through the NF-kB and MAPK pathways.

Entrez Gene

Summary

This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000167207:
This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. [provided by RefSeq, Jul 2008]

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada),
the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia)
and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health
through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database.
Contact: innatedb-mail@sfu.ca